The proposed project seeks to determine the manner in which genetically mediated psychological and metabolic factors influence risk for anorexia nervosa (AN) using a prospective longitudinal design. AN is a disorder of considerable public health importance due to high chronicity, low recovery rates, high mortality, and significant individual and family costs. Despite years of research, we still understand little about the pathophysiology of AN, hampering the development of pharmacological interventions and early intervention strategies. Recent findings from our investigative team suggest that body mass, metabolic factors, and growth patterns might not only prospectively predict AN onset, but also might reflect underlying genetic contributions of these parameters to illness risk. Extending these findings, the overarching aims of our proposed research are: first, to test if high genetic risk for AN and low genetic risk for obesity (using polygenic risk scores) are associated with a broad and narrow AN phenotypes; second, to examine associations between these polygenic risk scores and metabolic, growth, and body composition patterns prior to AN onset; and third, to determine whether high genetic risk for AN and low genetic risk for obesity are associated with severity and persistence of AN. We will leverage the considerable wealth of existing data in the Avon Longitudinal Study of Parents and Children (ALSPAC), a longitudinal population-based cohort that includes existing genome-wide, metabolic, growth, body composition data, as well as data on AN behaviours and AN diagnoses with measurements from before birth to age 25 on ~7,000 individuals. Our findings will clarify the developmental pathophysiology of AN, contribute to deepening the understanding of the biology and genetics of the illness, and potentially inform the development of effective approaches to treatment of this too often lethal illness.